Nerve Repair Using Decellularized Nerve Grafts in Rat Models. A Review of the Literature

Abstract

Peripheral nerve regeneration after severe traumatic nerve injury is a relevant clinical problem. Several different strategies have been investigated to solve the problem of bridging the nerve gap. Among these, the use of decellularized nerve grafts has been proposed as an alternative to auto/isografts, which represent the current gold standard in the treatment of severe nerve injury. This study reports the results of a systematic review of the literature published between January 2007 and October 2017. The aim was to quantitatively analyze the effectiveness of decellularized nerve grafts in rat experimental models. The review included 33 studies in which eight different decellularization protocols were described. The decellularized nerve grafts were reported to be immunologically safe and able to support both functional and morphological regeneration after nerve injury. Chemical protocols were found to be superior to physical protocols. However, further research is needed to optimize preparation protocols, including recellularization, improve their effectiveness, and substitute the current gold standard, especially in the repair of long nerve defects.

Detergent‐based decellularized peripheral nerve allografts: An in vivo preclinical study in the rat sciatic nerve injury model

“…These findings are in agreement with previous studies, where autograft technique showed a higher percentage of autotomy than those observed with the use of engineered substitutes (Carriel et al, 2013; Chato‐Astrain et al, 2018). However, the autograft technique showed, in all cases, better tissue regeneration, functional recovery, and muscle reinnervation (electromyography) than engineered (Chato‐Astrain et al, 2018) and DPNAs (Lovati et al, 2018; Whitlock et al, 2009). Therefore, it is probably that autotomy observed is a consequence of sensory loss, local discomfort, and paresthesia, being this information supported by the experimental and clinical literature (Argyriou, Koltzenburg, Polychronopoulos, Papapetropoulos, & Kalofonos, 2008; Geuna, 2015; Stang, Stollwerck, Prommersberger, & van Schoonhoven, 2013; Wall et al, 1979).…”

“…Clinical and functional assessments are an essential quality control in PN TE (Carriel, Garzon, et al, 2014; Vleggeert‐Lankamp, 2007). In general, in the rat sciatic nerve injury model, these analyses are performed weeks or months after surgery (10–15 weeks) where a partial regeneration and functional recovery occurs but which allows determining clear differences between different experimental conditions (Carriel et al, 2013; Carriel, Garzon, Campos, et al, 2017; Chato‐Astrain et al, 2018; Geuna, 2015; Lovati et al, 2018). The injury model used results in significant impairment of the lower limb, being the development of neurotrophic ulcers, nails loss, and autotomy the most frequent and well‐known drawbacks associated to this model (Geuna, 2015; Krsljak & Stajčić, 2004).…”

“…Through the removal of the cell compounds, it is possible to generate natural, properly organized and a tissue‐specific extracellular matrix (ECM) for a wide range of applications (Carriel, Alaminos, et al, 2014; Philips, Cornelissen, & Carriel, 2018). In this sense, several studies attempt to generate decellularized peripheral nerve allografts (DPNAs) (Lovati et al, 2018; Philips et al, 2018; Philips, Cornelissen, & Carriel, 2018), being the methods described by Sondell (Sondell, Lundborg, & Kanje, 1998) and Hudson et al (Hudson, Liu, & Schmidt, 2004) the most widely studied (Lovati et al, 2018; Philips, Cornelissen, & Carriel, 2018). In general, most of the recent literature reaffirm that detergent‐based decellularization techniques remain as one of the most efficient and used methods to remove the cellular component from a wide range of tissues, including PNs (Lovati et al, 2018; Philips, Cornelissen, & Carriel, 2018; Roosens et al, 2016; Shin, Park, & Kim, 2019) or for the generation of natural‐based hydrogels (Buckenmeyer, Meder, Prest, & Brown, 2019).…”

“…In this sense, the preservation of the ECM was improved by the combination of sulfobetaine‐10 (SB‐10) and sulfobetaine‐16 (SB‐16) with Triton X‐200. This method served to generate a commercially available DPNA, the Avance® Nerve Graft (AxoGen, Inc), which showed promising results (Giusti et al, 2012; Lovati et al, 2018). In this regard, a recent ex vivo and in vivo study concluded that the combination of amphoteric detergent and nuclease is an effective strategy to efficiently remove the cells and preserve the complex PNs ECM (Shin et al, 2019).…”

Regenerative Potential of Platelet-Rich Fibrin Releasate Combined with Adipose Tissue–Derived Stem Cells in a Rat Sciatic Nerve Injury Model

“…Numerous tests exist for evaluating nerve regeneration in experimental animal models, and they can be assessed in different ways 37 . We performed transection injuries and measured recovery by ladder rung walking test because it assesses the combination of motor and sensory function 22 , 38 – 42 and correlates with the sciatic functional index (SFI) 43 . Though SFI is generally considered to be accurate and reliable in describing sciatic nerve function 43 , it has certain disadvantages including frequent footprint artifacts and distortions produced by smearing of the ink when applied to the rats’ paws 44 .…”